NK cells: An attractive candidate for cancer therapy

Valipour, Behnaz; Velaei, Kobra; Abedelahi, Ali; Karimipour, Mohammad; Darabi, Masoud; Charoudeh, Hojjatollah Nozad

doi:10.1002/jcp.28657

Cited by 56 publications

(42 citation statements)

References 131 publications

(236 reference statements)

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“…It is well known that immunity decreases with aging and the number of immune cells in cancer patients changes with the development of the disease [25,26]. In the present study, we found that the circulating NK cells were positively correlated to the T and B lymphocytes, which are important immune cells of the human immune system [5][6][7]. Furthermore, we observed that the NK cell percentage was negatively correlated to the patient' age and ALB levels, suggesting that this prognostic indicator may collaborate with other immune indicators in CRC and decrease with aging.…”

Section: Discussionsupporting

confidence: 60%

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Prognostic value of peripheral blood natural killer cells in colorectal cancer

Tang

Xie

et al. 2020

BMC Gastroenterol

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Background: The association between natural killer (NK) cells and survival in colorectal cancer (CRC) patients remains controversial. This study aimed to clarify the prognostic value of peripheral blood NK cells in CRC patients.Methods: A total of 447 CRC patients who underwent radical surgery and chemotherapy were retrospectively analyzed. Cox regression analyses were used to identify independent prognostic indicators. Correlation between NK cell percentage and other clinicopathological features (gender, age, histological grade, tumor stage, immune cells, and inflammatory indicators) was analyzed. The prognostic values of the combinations of NK cell percentage and other clinicopathological features were also determined. Results: Multivariate Cox regression analysis revealed that NK cell percentage in the peripheral blood was an independent prognostic indicator in CRC patients. A higher percentage of NK cells indicated a longer survival time than a lower percentage. NK cell percentage was positively correlated to the T and B lymphocyte counts and negatively correlated to the patients' age and albumin levels. With an area of 0.741 under a receiver operating characteristic curve, NK cells have a moderate predictive value for 3rd-year survival in CRC. This area increased to 0.851 by combining NK cell percentage with the B lymphocyte count. Elderly patients and those at an advanced clinical stage presented a lower percentage of NK cells than younger patients and those at an early clinical stage.Conclusions: This study demonstrated that NK cells in the blood were an independent predictor of survival in CRC patients, and the combined count of NK cells and B lymphocytes could increase the prognostic value.

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Section: Discussionsupporting

confidence: 60%

“…Among these, the T lymphocytes, B lymphocytes, and natural killer (NK) cells form a vital component of the host antitumor immune response. These cells play crucial roles in the initiation, development, and progression of cancers [5][6][7]. They are also considered as potential targets in immunotherapy and clinical biomarker research [8].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of peripheral blood natural killer cells in colorectal cancer

Tang

Xie

et al. 2020

BMC Gastroenterol

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“…Furthermore, we added NK cells, components of the innate immune branch exerting a cytotoxic action without the need of prior antigen exposure 88,89 . The potential of NK cells in cancer immunotherapy has been pointed out by numerous preclinical studies that showed several attractive features of these cells 90 . Above all, NK cells display an overall safe profile, given by their limited in vivo persistence, the lack of clonal expansion, and the absence of the immune rejection associated with allogeneic transplantation 91 .…”

Section: Discussionmentioning

confidence: 99%

A QSP model of prostate cancer immunotherapy to identify effective combination therapies

Coletti

Leonardelli

Parolo

et al. 2020

Sci Rep

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dependent on androgen signaling, androgen deprivation therapy, either by chemical or surgical castration, is the first-line treatment for advanced PCa 40. Although this therapy is initially highly effective in most of the patients, in some cases the tumor evolves into an androgen independent form that currently lacks efficacious therapeutic options 41. The transition from the androgen dependent to the androgen independent state may occur through several mechanisms that are not yet completely understood 42. In this context, immunotherapy represents a highly promising new treatment approach. Over the last few years, numerous pre-clinical and clinical studies have been performed to develop and test different PCa immunotherapies 43. A main achievement has been the US Food and Drug Administration (FDA) approval of sipuleucel-T, so far the only approved immunotherapy for PCa treatment 40. Compared with other types of cancer, PCa is relatively insensitive to the most popular immunotherapies and additional studies are needed to understand the mechanisms underlying this lack of immune responsiveness 44. Thus, evaluating combination therapies is another important step to improve therapeutic benefits 45. We herein propose a QSP model of prostate cancer that extends a previous one published by Peng et al. 46 based on data from a murine Pten prostate cancer model 47,48. Although Peng and coworkers already described the action of CTLs, dendritic cells, Tregs, androgens and interleukin-2 (IL-2) in the tumor microenvironment, we extended the characterization of the immune system by including MDSCs and Natural Killer (NK) cells as potential targets for new prostate cancer therapies. The main goal of this contribution is, indeed, to provide a mathematical model able to test the efficacy of several immunotherapies and their combinations. We incorporate a wide range of experimental data from literature 31,46,49-51 to implement seven treatments. The efficacy of therapies is assessed considering the model-predicted tumor inhibitory effect and the synergy of combination therapies. Synergy between treatments plays a crucial role to reduce the dosage of each drug maintaining a satisfactory overall treatment efficacy, improving patients' quality of life 52. The paper is organized as follows. In the result section we provide a description of the model diagram and a detailed explanation of the Ordinary Differential Equations (ODEs) constituting the mathematical model. We provide the model simulations to verify the reproducibility of the experimental data and to compare the predicted outcomes with known biological mechanisms. We identify the most effective treatment combinations for prostate cancer through the model-predicted tumor size and the treatment synergy. Moreover, we emphasize the androgen deprivation therapy as leading treatment in a decision tree to choose the best protocol to treat androgen independent prostate cancer. Finally, a discussion of the results and a description of the study limitations is provided. Results The mathema...

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“…Natural killer (NK) cells, which account for 10%–15% of the circulating lymphocytes in the innate immune system, can spontaneously lyse tumor cells without requiring prior sensitization [ 46 ]; therefore, NK cells have unique roles in cancer immune surveillance and clearance [ 47 , 48 ]. Following activation counterbalanced by various receptors, NK cells express activating receptors, including natural cytotoxicity receptors (e.g., NKp30 and NKp44) and Fc-gamma receptors (e.g., CD16), that recognize tumor cells or virus-infected cells [ 49 ].…”

Section: Nanoparticle Facilitates the Killing Ability Of Natural Killmentioning

confidence: 99%

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells

Wang

et al. 2020

Acta Pharmacol Sin

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Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy.

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NK cells: An attractive candidate for cancer therapy

Cited by 56 publications

References 131 publications

Prognostic value of peripheral blood natural killer cells in colorectal cancer

Prognostic value of peripheral blood natural killer cells in colorectal cancer

A QSP model of prostate cancer immunotherapy to identify effective combination therapies

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells

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